Browsing by Subject "Sepsis"

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  • Bellomo, Rinaldo; Kellum, John A.; Ronco, Claudio; Wald, Ron; Martensson, Johan; Maiden, Matthew; Bagshaw, Sean M.; Glassford, Neil J.; Lankadeva, Yugeesh; Vaara, Suvi; Schneider, Antoine (2017)
    Acute kidney injury (AKI) and sepsis carry consensus definitions. The simultaneous presence of both identifies septic AKI. Septic AKI is the most common AKI syndrome in ICU and accounts for approximately half of all such AKI. Its pathophysiology remains poorly understood, but animal models and lack of histological changes suggest that, at least initially, septic AKI may be a functional phenomenon with combined microvascular shunting and tubular cell stress. The diagnosis remains based on clinical assessment and measurement of urinary output and serum creatinine. However, multiple biomarkers and especially cell cycle arrest biomarkers are gaining acceptance. Prevention of septic AKI remains based on the treatment of sepsis and on early resuscitation. Such resuscitation relies on the judicious use of both fluids and vasoactive drugs. In particular, there is strong evidence that starch-containing fluids are nephrotoxic and decrease renal function and suggestive evidence that chloride-rich fluid may also adversely affect renal function. Vasoactive drugs have variable effects on renal function in septic AKI. At this time, norepinephrine is the dominant agent, but vasopressin may also have a role. Despite supportive therapies, renal function may be temporarily or completely lost. In such patients, renal replacement therapy (RRT) becomes necessary. The optimal intensity of this therapy has been established, while the timing of when to commence RRT is now a focus of investigation. If sepsis resolves, the majority of patients recover renal function. Yet, even a single episode of septic AKI is associated with increased subsequent risk of chronic kidney disease.
  • FINNAKI Study Grp (2019)
    Background Injury to endothelium and glycocalyx predisposes to vascular leak, which may subsequently lead to increased fluid requirements and worse outcomes. In this post hoc study of the prospective multicenter observational Finnish Acute Kidney Injury (FINNAKI) cohort study conducted in 17 Finnish intensive care units, we studied the association of Syndecan-1 (SDC-1), Angiopoetin-2 (Ang-2), soluble thrombomodulin (sTM), vascular adhesion protein-1 (VAP-1) and interleukin-6 (IL-6) with fluid administration and balance among septic critical care patients and their association with development of acute kidney injury (AKI) and 90-day mortality. Results SDC-1, Ang-2, sTM, VAP-1 and IL-6 levels were measured at ICU admission from 619 patients with sepsis. VAP-1 decreased (p <0.001) and IL-6 increased (p <0.001) with increasing amounts of administered fluid, but other biomarkers did not show differences according to fluid administration. In linear regression models adjusted for IL-6, only VAP-1 was significantly associated with fluid administration on day 1 (p <0.001) and the cumulative fluid balance on day 5/ICU discharge (p = 0.001). Of 415 patients admitted without AKI, altogether 112 patients (27.0%) developed AKI > 12 h from ICU admission (AKI(>12 h)). They had higher sTM levels than patients without AKI, and after multivariable adjustment log, sTM level was associated with AKI(>12 h) with OR (95% CI) of 12.71 (2.96-54.67), p = 0.001). Ninety-day non-survivors (n = 180; 29.1%) had higher SDC-1 and sTM levels compared to survivors. After adjustment for known confounders, log SDC-1 (OR [95% CI] 2.13 [1.31-3.49], p = 0.002), log sTM (OR [95% CI] 7.35 [2.29-23.57], p <0.001), and log Ang-2 (OR [95% CI] 2.47 [1.44-4.14], p = 0.001) associated with an increased risk for 90-day mortality. Finally, patients who had high levels of all three markers, namely, SDC-1, Ang-2 and sTM, had an adjusted OR of 5.61 (95% CI 2.67-11.79; p <0.001) for 90-day mortality. Conclusions VAP-1 and IL-6 associated with fluid administration on the first ICU day. After adjusting for confounders, sTM was associated with development of AKI after 12 h from ICU admission. SDC-1, Ang-2 and sTM were independently associated with an increased risk for 90-day mortality.
  • Inkinen, Nina; Pettilä, Ville; Lakkisto, Päivi; Kuitunen, Anne; Jukarainen, Sakari; Bendel, Stepani; Inkinen, Outi; Ala-Kokko, Tero; Vaara, Suvi T. (Springer International Publishing, 2019)
    Abstract Background Injury to endothelium and glycocalyx predisposes to vascular leak, which may subsequently lead to increased fluid requirements and worse outcomes. In this post hoc study of the prospective multicenter observational Finnish Acute Kidney Injury (FINNAKI) cohort study conducted in 17 Finnish intensive care units, we studied the association of Syndecan-1 (SDC-1), Angiopoetin-2 (Ang-2), soluble thrombomodulin (sTM), vascular adhesion protein-1 (VAP-1) and interleukin-6 (IL-6) with fluid administration and balance among septic critical care patients and their association with development of acute kidney injury (AKI) and 90-day mortality. Results SDC-1, Ang-2, sTM, VAP-1 and IL-6 levels were measured at ICU admission from 619 patients with sepsis. VAP-1 decreased (p < 0.001) and IL-6 increased (p < 0.001) with increasing amounts of administered fluid, but other biomarkers did not show differences according to fluid administration. In linear regression models adjusted for IL-6, only VAP-1 was significantly associated with fluid administration on day 1 (p < 0.001) and the cumulative fluid balance on day 5/ICU discharge (p = 0.001). Of 415 patients admitted without AKI, altogether 112 patients (27.0%) developed AKI > 12 h from ICU admission (AKI>12 h). They had higher sTM levels than patients without AKI, and after multivariable adjustment log, sTM level was associated with AKI>12 h with OR (95% CI) of 12.71 (2.96–54.67), p = 0.001). Ninety-day non-survivors (n = 180; 29.1%) had higher SDC-1 and sTM levels compared to survivors. After adjustment for known confounders, log SDC-1 (OR [95% CI] 2.13 [1.31–3.49], p = 0.002), log sTM (OR [95% CI] 7.35 [2.29–23.57], p < 0.001), and log Ang-2 (OR [95% CI] 2.47 [1.44–4.14], p = 0.001) associated with an increased risk for 90-day mortality. Finally, patients who had high levels of all three markers, namely, SDC-1, Ang-2 and sTM, had an adjusted OR of 5.61 (95% CI 2.67–11.79; p < 0.001) for 90-day mortality. Conclusions VAP-1 and IL-6 associated with fluid administration on the first ICU day. After adjusting for confounders, sTM was associated with development of AKI after 12 h from ICU admission. SDC-1, Ang-2 and sTM were independently associated with an increased risk for 90-day mortality.
  • Lankelma, Jacqueline M.; van Vught, Lonneke A.; Belzer, Clara; Schultz, Marcus J.; van der Poll, Tom; de Vos, Willem M.; Wiersinga, W. Joost (2017)
    The intestinal microbiota has emerged as a virtual organ with essential functions in human physiology. Antibiotic-induced disruption of the microbiota in critically ill patients may have a negative influence on key energy resources and immunity. We set out to characterize the fecal microbiota composition in critically ill patients both with and without sepsis and to explore the use of microbiota-derived markers for clinical outcome measurements in this setting. In this prospective observational cohort study we analyzed the fecal microbiota of 34 patients admitted to the intensive care unit. Fifteen healthy subjects served as controls. The fecal microbiota was phylogenetically characterized by 16S rRNA gene sequencing, and associations with clinical outcome parameters were evaluated. A marked shift in fecal bacterial composition was seen in all septic and non-septic critically ill patients compared with controls, with extreme interindividual differences. In 13 of the 34 patients, a single bacterial genus made up > 50% of the gut microbiota; in 4 patients this was even > 75%. A significant decrease in bacterial diversity was observed in half of the patients. No associations were found between microbiota diversity, Firmicutes/Bacteroidetes ratio, or Gram-positive/Gram-negative ratio and outcome measurements such as complications and survival. We observed highly heterogeneous patterns of intestinal microbiota in both septic and non-septic critically ill patients. Nevertheless, some general patterns were observed, including disappearance of bacterial genera with important functions in host metabolism. More detailed knowledge of the short- and long-term health consequences of these major shifts in intestinal bacterial communities is needed.
  • Perner, Anders; Cecconi, Maurizio; Cronhjort, Maria; Darmon, Michael; Jakob, Stephan M.; Pettilä, Ville; van der Horst, Iwan C. C. (2018)
    Hypovolemia is frequent in patients with sepsis and may contribute to worse outcome. The management of these patients is impeded by the low quality of the evidence for many of the specific components of the care. In this paper, we discuss recent advances and controversies in this field and give expert statements for the management of hypovolemia in patients with sepsis including triggers and targets for fluid therapy and volumes and types of fluid to be given. Finally, we point to unanswered questions and suggest a roadmap for future research.
  • Perner, Anders; Prowle, John; Joannidis, Michael; Young, Paul; Hjortrup, Peter B.; Pettilä, Ville (2017)
    Acute kidney injury (AKI) and fluids are closely linked through oliguria, which is a marker of the former and a trigger for administration of the latter. Recent progress in this field has challenged the physiological and clinical rational of using oliguria as a trigger for the administration of fluid and brought attention to the delicate balance between benefits and harms of different aspects of fluid management in critically ill patients, in particular those with AKI. This narrative review addresses various aspects of fluid management in AKI outlining physiological aspects, the effects of crystalloids and colloids on kidney function and the effect of various resuscitation and de-resuscitation strategies on the course and outcome of AKI.
  • ARISE Investigators; Luethi, Nora; Bailey, Michael; Harjola, V-P; Okkonen, M.; Pettilä, V.; Sutinen, E.; Wilkman, E. (2020)
    Purpose: To assess the impact of gender and pre-menopausal state on short- and long-term outcomes in patients with septic shock. Material and methods: Cohort study of the Australasian Resuscitation in Sepsis Evaluation (ARISE) trial, an international randomized controlled trial comparing early goal-directed therapy (EGDT) to usual care in patients with early septic shock, conducted between October 2008 and April 2014. The primary exposure in this analysis was legal gender and the secondary exposure was pre-menopausal state defined by chronological age ( Results: 641 (40.3%) of all 1591 ARISE trial participants in the intention-to-treat population were females and overall, 337 (21.2%) (146 females) patients were 50 years of age or younger. After risk-adjustment, we could not identify any survival benefit for female patients at day 90 in the younger (50 years) age-group (aOR: 1.10 (0.81-1.49), p = .56). Similarly, there was no gender-difference in ICU, hospital, 1-year mortality nor quality of life measures. Conclusions: This post-hoc analysis of a large multi-center trial in early septic shock has shown no short- or long-term survival effect for women overall as well as in the pre-menopausal age-group. (C) 2019 Elsevier Inc. All rights reserved.
  • Vilander, Laura; Kaunisto, Mari A.; Vaara, Suvi; Pettila, Ville; FINNAKI Study Grp (2017)
    Background: Acute kidney injury (AKI) is a multifactorial syndrome, but knowledge about its pathophysiology and possible genetic background is limited. Recently the first hypothesis-free genetic association studies have been published to explore individual susceptibility to AKI. We aimed to replicate the previously identified associations between five candidate single nucleotide polymorphisms (SNP) in apoptosis-related genes BCL2, SERPINA4, SERPINA5, and SIK3 and the development of AKI, using a prospective cohort of critically ill patients with sepsis/ septic shock, in Finland. Methods: This is a prospective, observational multicenter study. Of 2567 patients without chronic kidney disease and with genetic samples included in the Finnish Acute Kidney Injury (FINNAKI) study, 837 patients had sepsis and 627 patients had septic shock. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, considering stages 2 and 3 affected (severe AKI), stage 0 unaffected, and stage 1 indecisive. Genotyping was done using iPLEX (TM) Assay (Agena Bioscience). The genotyped SNPs were rs8094315 and rs12457893 in the intron of the BCL2 gene, rs2093266 in the SERPINA4 gene, rs1955656 in the SERPINA5 gene and rs625145 in the SIK3 gene. Association analyses were performed using logistic regression with PLINK software. Results: We found no significant associations between the SNPs and severe AKI in patients with sepsis/ septic shock, even after adjustment for confounders. Among patients with septic shock (252 with severe AKI and 226 without AKI (149 with KDIGO stage 1 excluded)), the SNPs rs2093266 and rs1955656 were significantly (odds ratio 0.63, p = 0.04276) associated with stage 2-3 AKI after adjusting for clinical and demographic variables. Conclusions: The SNPs rs2093266 in the SERPINA4 and rs1955656 in the SERPINA5 were associated with the development of severe AKI (KDIGO stage 2-3) in critically ill patients with septic shock. For the other SNPs, we did not confirm the previously reported associations.
  • Vilander, Laura M.; Kaunisto, Mari A.; Vaara, Suvi T.; Pettilä, Ville (BioMed Central, 2017)
    Abstract Background Acute kidney injury (AKI) is a multifactorial syndrome, but knowledge about its pathophysiology and possible genetic background is limited. Recently the first hypothesis-free genetic association studies have been published to explore individual susceptibility to AKI. We aimed to replicate the previously identified associations between five candidate single nucleotide polymorphisms (SNP) in apoptosis-related genes BCL2, SERPINA4, SERPINA5, and SIK3 and the development of AKI, using a prospective cohort of critically ill patients with sepsis/septic shock, in Finland. Methods This is a prospective, observational multicenter study. Of 2567 patients without chronic kidney disease and with genetic samples included in the Finnish Acute Kidney Injury (FINNAKI) study, 837 patients had sepsis and 627 patients had septic shock. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, considering stages 2 and 3 affected (severe AKI), stage 0 unaffected, and stage 1 indecisive. Genotyping was done using iPLEXTM Assay (Agena Bioscience). The genotyped SNPs were rs8094315 and rs12457893 in the intron of the BCL2 gene, rs2093266 in the SERPINA4 gene, rs1955656 in the SERPINA5 gene and rs625145 in the SIK3 gene. Association analyses were performed using logistic regression with PLINK software. Results We found no significant associations between the SNPs and severe AKI in patients with sepsis/septic shock, even after adjustment for confounders. Among patients with septic shock (252 with severe AKI and 226 without AKI (149 with KDIGO stage 1 excluded)), the SNPs rs2093266 and rs1955656 were significantly (odds ratio 0.63, p = 0.04276) associated with stage 2–3 AKI after adjusting for clinical and demographic variables. Conclusions The SNPs rs2093266 in the SERPINA4 and rs1955656 in the SERPINA5 were associated with the development of severe AKI (KDIGO stage 2–3) in critically ill patients with septic shock. For the other SNPs, we did not confirm the previously reported associations.
  • Sartelli, Massimo; Abu-Zidan, Fikri M.; Catena, Fausto; Griffiths, Ewen A.; Di Saverio, Salomone; Coimbra, Raul; Ordonez, Carlos A.; Leppaniemi, Ari; Fraga, Gustavo P.; Coccolini, Federico; Agresta, Ferdinando; Abbas, Asrhaf; Kader, Saleh Abdel; Agboola, John; Amhed, Adamu; Ajibade, Adesina; Akkucuk, Seckin; Alharthi, Bandar; Anyfantakis, Dimitrios; Augustin, Goran; Baiocchi, Gianluca; Bala, Miklosh; Baraket, Oussama; Bayrak, Savas; Bellanova, Giovanni; Beltran, Marcelo A.; Bini, Roberto; Boal, Matthew; Borodach, Andrey V.; Bouliaris, Konstantinos; Branger, Frederic; Brunelli, Daniele; Catani, Marco; Jusoh, Asri Che; Chichom-Mefire, Alain; Cocorullo, Gianfranco; Colak, Elif; Costa, David; Costa, Silvia; Cui, Yunfeng; Curca, Geanina Loredana; Curry, Terry; Das, Koray; Delibegovic, Samir; Demetrashvili, Zaza; Di Carlo, Isidoro; Drozdova, Nadezda; El Zalabany, Tamer; Enani, Mushira Abdulaziz; Faro, Mario; Gachabayov, Mahir; Gimenez Maurel, Teresa; Gkiokas, Georgios; Gomes, Carlos Augusto; Teixeira Gonsaga, Ricardo Alessandro; Guercioni, Gianluca; Guner, Ali; Gupta, Sanjay; Gutierrez, Sandra; Hutan, Martin; Ioannidis, Orestis; Isik, Arda; Izawa, Yoshimitsu; Jain, Sumita A.; Jokubauskas, Mantas; Karamarkovic, Aleksandar; Kauhanen, Saila; Kaushik, Robin; Kenig, Jakub; Khokha, Vladimir; Il Kim, Jae; Kong, Victor; Koshy, Renol; Krasniqi, Avidyl; Kshirsagar, Ashok; Kuliesius, Zygimantas; Lasithiotakis, Konstantinos; Leao, Pedro; Lee, Jae Gil; Leon, Miguel; Lizarazu Perez, Aintzane; Lohsiriwat, Varut; Lopez-Tomassetti Fernandez, Eudaldo; Lostoridis, Eftychios; Mn, Raghuveer; Major, Piotr; Marinis, Athanasios; Marrelli, Daniele; Martinez-Perez, Aleix; Marwah, Sanjay; McFarlane, Michael; Melo, Renato Bessa; Mesina, Cristian; Michalopoulos, Nick; Moldovanu, Radu; Mouaqit, Ouadii; Munyika, Akutu; Negoi, Ionut; Nikolopoulos, Ioannis; Nita, Gabriela Elisa; Olaoye, Iyiade; Omari, Abdelkarim; Rodriguez Ossa, Paola; Ozkan, Zeynep; Padmakumar, Ramakrishnapillai; Pata, Francesco; Pereira Junior, Gerson Alves; Pereira, Jorge; Pintar, Tadeja; Pouggouras, Konstantinos; Prabhu, Vinod; Rausei, Stefano; Rems, Miran; Rios-Cruz, Daniel; Sakakushev, Boris; Luisa Sanchez de Molina, Maria; Seretis, Charampolos; Shelat, Vishal; Simoes, Romeo Lages; Sinibaldi, Giovanni; Skrovina, Matej; Smirnov, Dmitry; Spyropoulos, Charalampos; Tepp, Jaan; Tezcaner, Tugan; Tolonen, Matti; Torba, Myftar; Ulrych, Jan; Uzunoglu, Mustafa Yener; van Dellen, David; van Ramshorst, Gabrielle H.; Vasquez, Giorgio; Venara, Aurelien; Vereczkei, Andras; Vettoretto, Nereo; Vlad, Nutu; Yadav, Sanjay Kumar; Yilmaz, Tonguc Utku; Yuan, Kuo-Ching; Zachariah, Sanoop Koshy; Zida, Maurice; Zilinskas, Justas; Ansaloni, Luca (2015)
    Background: To validate a new practical Sepsis Severity Score for patients with complicated intra-abdominal infections (cIAIs) including the clinical conditions at the admission (severe sepsis/septic shock), the origin of the cIAIs, the delay in source control, the setting of acquisition and any risk factors such as age and immunosuppression. Methods: The WISS study (WSES cIAIs Score Study) is a multicenter observational study underwent in 132 medical institutions worldwide during a four-month study period (October 2014-February 2015). Four thousand five hundred thirty-three patients with a mean age of 51.2 years (range 18-99) were enrolled in the WISS study. Results: Univariate analysis has shown that all factors that were previously included in the WSES Sepsis Severity Score were highly statistically significant between those who died and those who survived (p <0.0001). The multivariate logistic regression model was highly significant (p <0.0001, R-2 = 0.54) and showed that all these factors were independent in predicting mortality of sepsis. Receiver Operator Curve has shown that the WSES Severity Sepsis Score had an excellent prediction for mortality. A score above 5.5 was the best predictor of mortality having a sensitivity of 89.2 %, a specificity of 83.5 % and a positive likelihood ratio of 5.4. Conclusions: WSES Sepsis Severity Score for patients with complicated Intra-abdominal infections can be used on global level. It has shown high sensitivity, specificity, and likelihood ratio that may help us in making clinical decisions.
  • Saarinen, Petri (Helsingfors universitet, 2014)
    Enterococci is a group of gram positive bacteria part of human intestinal flora. While generally harmless, several species of the group are known to cause severe infections in humans, including bloodstream infections leading to sepsis. Since Enterococci are naturally resistant to many antibiotics, the use of glycopeptides, considered a”last resort” drugs, is common in treatment of enterococcal infections. In recent years, however, the emergence of glycopeptide resistant Enterococci (GRE) has been an increasing concern for clinics and microbiology laboratories around the world, creating a need for fast and accurate screening tests differentiating the glycopeptide resistant Enterococcus strains from the non-resistant ones. In this study, a combined PCR and microarray hybridization based method for identification of the clinically most prevalent GRE was established as a part of commercial sepsis diagnostic test called Prove-it™ Sepsis. Already identifying the most common Enterococcus species (E.faecium and E.faecalis), the detection of glycopeptide resistance causing ligase genes vanA and vanB and species level identification of intrinsically glycopeptide resistant E.gallinarum and E.casseliflavus were added as part of the the test. Primers were designed for sequencing vanA and vanB genes and multiple strains, provided by a Finnish clinical laboratory Huslab, were sequenced. Sequence regions unique to these genes were identified according to sequence alignment data containing the sequenced gene regions and other relevant sequences found in public sequence databases. Based on these data, primers were designed for the amplification of the selected gene regions. For identification of the amplified gene regions, a set of hybridization probes were designed and printed on microarray. In addition, probes for identifying E.casseliflavus and E.gallinarum were designed based on sequence aligment data gathered from Mobidiag Ltd. private biobank. The identification of these species was based on topoisomerase encoding gyrB gene amplified by the Prove-it™ Sepsis broad range PCR. Several primers for the amplification of vanA and vanB genes were designed and one primer pair for each was selected to be integrated to the Prove-it™ Sepsis multiplex-PCR. Similarily, multiple hybridization probes were designed for detecting vanA, vanB, E.casseliflavus and E. gallinarum. Four probes for each target gene region were selected to be integrated to the commercial test. With this modified test, 12 pure culture samples of clinical origin were tested and the results were compared to the ones provided by the laboratory of clinical microbiology of Hôspital de bicêtre (Paris, France). Results provided by the modified PCR and microarray test were identical to the reference results in 11 out of 12 cases.
  • Tverring, Jonas; Vaara, Suvi T.; Fisher, Jane; Poukkanen, Meri; Pettila, Ville; Linder, Adam; FINNAKI Study Grp (2017)
    Background: Sepsis-related acute kidney injury (AKI) accounts for major morbidity and mortality among the critically ill. Heparin-binding protein (HBP)is a promising biomarker in predicting development and prognosis of severe sepsis and septic shock that has recently been proposed to be involved in the pathophysiology of AKI. The objective of this study was to investigate the added predictive value of measuring plasma HBP on admission to the intensive care unit (ICU) regarding the development of septic AKI. Methods: We included 601 patients with severe sepsis or septic shock from the prospective, observational FINNAKI study conducted in seventeen Finnish ICUs during a 5-month period (1 September 2011-1 February 2012). The main outcome measure was the development of KDIGO AKI stages 2-3 from 12 h after admission up to 5 days. Statistical analysis for the primary endpoint included construction of a clinical risk model, area under the receiver operating curve (ROC area), category-free net reclassification index (cfNRI) and integrated discrimination improvement (IDI) with 95% confidence intervals (95% CI). Results: Out of 511 eligible patients, 101 (20%) reached the primary endpoint. The addition of plasma HBP to a clinical risk model significantly increased ROC area (0.82 vs. 0.78, p = 0.03) and risk classification scores: cfNRI 62.0% (95% CI 40.5-82.4%) and IDI 0.053 (95% CI 0.029-0.075). Conclusions: Plasma HBP adds predictive value to known clinical risk factors in septic AKI. Further studies are warranted to compare the predictive performance of plasma HBP to other novel AKI biomarkers.
  • Efraim Investigators; Nine-I Study Grp; Martin-Loeches, Ignacio; Valkonen, Miia; Azoulay, Elie (2019)
    BackgroundIt is unclear whether influenza infection and associated co-infection are associated with patient-important outcomes in critically ill immunocompromised patients with acute respiratory failure.MethodsPreplanned secondary analysis of EFRAIM, a prospective cohort study of 68 hospitals in 16 countries. We included 1611 patients aged 18years or older with non-AIDS-related immunocompromise, who were admitted to the ICU with acute hypoxemic respiratory failure. The main exposure of interest was influenza infection status. The primary outcome of interest was all-cause hospital mortality, and secondary outcomes ICU length of stay (LOS) and 90-day mortality.ResultsInfluenza infection status was categorized into four groups: patients with influenza alone (n=95, 5.8%), patients with influenza plus pulmonary co-infection (n=58, 3.6%), patients with non-influenza pulmonary infection (n=820, 50.9%), and patients without pulmonary infection (n=638, 39.6%). Influenza infection status was associated with a requirement for intubation and with LOS in ICU (P
  • Martin-Loeches, Ignacio; Lemiale, Virginie; Geoghegan, Pierce; McMahon, Mary A; Pickkers, Peter; Soares, Marcio; Perner, Anders; Meyhoff, Tine S; Bukan, Ramin B; Rello, Jordi; Bauer, Philippe R; van de Louw, Andry; Taccone, Fabio S; Salluh, Jorge; Hemelaar, Pleun; Schellongowski, Peter; Rusinova, Katerina; Terzi, Nicolas; Mehta, Sangeeta; Antonelli, Massimo; Kouatchet, Achille; Klepstad, Pål; Valkonen, Miia; Landburg, Precious P; Barratt-Due, Andreas; Bruneel, Fabrice; Pène, Frédéric; Metaxa, Victoria; Moreau, Anne S; Souppart, Virginie; Burghi, Gaston; Girault, Christophe; Silva, Ulysses V A; Montini, Luca; Barbier, Francois; Nielsen, Lene B; Gaborit, Benjamin; Mokart, Djamel; Chevret, Sylvie; Azoulay, Elie (BioMed Central, 2019)
    Abstract Background It is unclear whether influenza infection and associated co-infection are associated with patient-important outcomes in critically ill immunocompromised patients with acute respiratory failure. Methods Preplanned secondary analysis of EFRAIM, a prospective cohort study of 68 hospitals in 16 countries. We included 1611 patients aged 18 years or older with non-AIDS-related immunocompromise, who were admitted to the ICU with acute hypoxemic respiratory failure. The main exposure of interest was influenza infection status. The primary outcome of interest was all-cause hospital mortality, and secondary outcomes ICU length of stay (LOS) and 90-day mortality. Results Influenza infection status was categorized into four groups: patients with influenza alone (n = 95, 5.8%), patients with influenza plus pulmonary co-infection (n = 58, 3.6%), patients with non-influenza pulmonary infection (n = 820, 50.9%), and patients without pulmonary infection (n = 638, 39.6%). Influenza infection status was associated with a requirement for intubation and with LOS in ICU (P < 0.001). Patients with influenza plus co-infection had the highest rates of intubation and longest ICU LOS. On crude analysis, influenza infection status was associated with ICU mortality (P < 0.001) but not hospital mortality (P = 0.09). Patients with influenza plus co-infection and patients with non-influenza infection alone had similar ICU mortality (41% and 37% respectively) that was higher than patients with influenza alone or those without infection (33% and 26% respectively). A propensity score-matched analysis did not show a difference in hospital mortality attributable to influenza infection (OR = 1.01, 95%CI 0.90–1.13, P = 0.85). Age, severity scores, ARDS, and performance status were all associated with ICU, hospital, and 90-day mortality. Conclusions Category of infectious etiology of respiratory failure (influenza, non-influenza, influenza plus co-infection, and non-infectious) was associated with ICU but not hospital mortality. In a propensity score-matched analysis, influenza infection was not associated with the primary outcome of hospital mortality. Overall, influenza infection alone may not be an independent risk factor for hospital mortality in immunosuppressed patients.
  • Hautala, Maria; Mikkonen, Kirsi; Helander, Heli (2022)
    • Kuumekouristuksen saaneelle lapselle tehdään tarkka kliininen arvio. Siinä huomioidaan keskushermostoinfektion, vakavan bakteeri-infektion ja muiden kouristelua provosoivien tekijöiden mahdollisuus. • Päivystyksellinen lähete erikoissairaanhoitoon tehdään ainakin, jos lapsi kouristeli yli 5 minuuttia, kuumekouristus oli monimuotoinen tai tajunnantaso jää alentuneeksi kohtauksen jälkeen. Lähete tehdään myös, jos epäillään keskushermostoinfektiota tai sepsistä tai lapsen yleistila sitä muuten vaatii. • Vanhempia informoidaan yksinkertaisen kuumekouristuksen hyvänlaatuisuu- desta, ja ensiapu ohjeistetaan huolellisesti.
  • Wallgren, Ulrika Margareta; Antonsson, Viktor Erik; Castren, Maaret; Kurland, Lisa (2016)
    Background: The presentation of sepsis is varied and our hypotheses were that septic patients with non-specific presentations such as decreased general condition (DGC) have a less favourable outcome, and that a screening tool could increase identification of these patients. We aimed to: 1) assess time to antibiotics and in-hospital mortality among septic patients with ED chief complaint DGC, as compared with septic patients with other ED chief complaints, and 2) determine whether a screening tool could improve identification of septic patients with non-specific presentations such as DGC. Methods: Cross sectional study comparing time to antibiotics (Mann Whitney and Kaplan-Meier tests), and in-hospital mortality (logistic regression), between 61 septic patients with ED chief complaint DGC and 516 septic patients with other ED chief complaints. The sensitivity and specificity of the modified Robson screening tool was compared with that of ED doctor clinical judgment (McNemar's two related samples test) among 122 patients presenting to the ED with chief complaint DGC, of which 61 were discharged with ICD code sepsis. Results: Septic patients presenting to the ED with the chief complaint DGC had a longer median time to antibiotics (05: 26 h: minutes; IQR 4: 00-10: 40, vs. 03: 56 h: minutes; IQR 2: 21-7: 32) and an increased in-hospital mortality (crude OR = 4.01; 95 % CI, 2.19-7.32), compared to septic patients with other ED chief complaints. This association remained significant when adjusting for sex, age, priority, comorbidity and fulfilment of the Robson score (OR 4.31; 95 % CI, 2.12-8.77). The modified Robson screening tool had a higher sensitivity (63.0 vs. 24.6 %, p <0.001), but a lower specificity (68.3 vs. 100.0 %, p <0.001), as compared to clinical judgment. Discussion: This is, to the best of our knowledge, the first study comparing outcome of septic patients according to ED chief complaint. Septic patients presenting with a non-specific ED presentation, here exemplified as the chief complaint DGC, have a less favourable outcome. Our results indicate that implementation of a screening tool may increase the identification of septic patients.
  • Sartelli, Massimo; Catena, Fausto; Abu-Zidan, Fikri M.; Ansaloni, Luca; Biffl, Walter L.; Boermeester, Marja A.; Ceresoli, Marco; Chiara, Osvaldo; Coccolini, Federico; De Waele, Jan J.; Di Saverio, Salomone; Eckmann, Christian; Fraga, Gustavo P.; Giannella, Maddalena; Girardis, Massimo; Griffiths, Ewen A.; Kashuk, Jeffry; Kirkpatrick, Andrew W.; Khokha, Vladimir; Kluger, Yoram; Labricciosa, Francesco M.; Leppäniemi, Ari; Maier, Ronald V.; May, Addison K.; Malangoni, Mark; Martin-Loeches, Ignacio; Mazuski, John; Montravers, Philippe; Peitzman, Andrew; Pereira, Bruno M.; Reis, Tarcisio; Sakakushev, Boris; Sganga, Gabriele; Soreide, Kjetil; Sugrue, Michael; Ulrych, Jan; Vincent, Jean-Louis; Viale, Pierluigi; Moore, Ernest E. (2017)
    This paper reports on the consensus conference on the management of intra-abdominal infections (IAIs) which was held on July 23, 2016, in Dublin, Ireland, as a part of the annual World Society of Emergency Surgery (WSES) meeting. This document covers all aspects of the management of IAIs. The Grading of Recommendations Assessment, Development and Evaluation recommendation is used, and this document represents the executive summary of the consensus conference findings.
  • Kuuliala, Krista; Louhimo, Johanna; Meri, Seppo (2020)
    Ohjelmoitunutta solukuolemaa tarvitaan elinten kehittymisessä, kudosten homeostaasin ja uusiutumiskyvyn ylläpidossa sekä puolustussolujen toiminnan säätelyssä. Sen ainoana muotona pidettiin pitkään kaspaasientsyymien säätelemää, tulehdusta lietsomatonta apoptoosia. Nykyään tiedetään, ettei tulehdus- ja soluvauriosignaalien laukaisema nekroosikaan ole vain kontrolloimaton solutuho, vaan siitä on aktivoitumiskykyisiä geneettisesti ohjelmoituneita muotoja, joista tunnetuin on nekroptoosi eli tulehduksellisesti ohjelmoitunut nekroottinen solukuolema. Keskeiset solunsisäisessä nekroptoosisignaloinnissa toimivat proteiinit ovat RIP (receptor-interacting protein kinase) 1, RIP3 ja MLKL (mixed lineage kinase domain-like protein). Niiden aktivoituessa, esimerkiksi virus- (muun muassa koronavirus) tai bakteeri-infektion yhteydessä, nekroptoottisesta solusta vapautuu vaarasignaalimolekyylejä. Nekroptoosi aiheuttaa tulehdusreaktion, jolla voi kudostuhon ohella olla regeneratiivisia vaikutuksia. Nekroptoositutkimus on avannut uusia näkymiä immuunipuolustuksen keinoihin ja tulehduksellisten sairauksien patogeneesiin sekä mahdollisuuksiin vaikuttaa näihin.
  • Vilander, Laura M. (2020)
    Genetic predisposition to acute kidney injury in critically ill adults. Laura Vilander, Helsingin yliopisto.
  • Lindström, Mikael; Valkonen, Miia; Tohmola, Niina; Renkonen, Risto; Strandin, Tomas; Vaheri, Antti; Itkonen, Outi (2019)
    Background: Bradykinin is an important mediator of inflammation and vascular permeability and could have an important role in the development of septic shock. Measurement of bradykinin by immunological methods may suffer from interference and lack of specificity. We developed and validated a liquid chromatography mass spectrometry assay (LC-MS/MS) for plasma bradykinin. Methods: We used plasma samples from healthy volunteers (n = 19) and patients with septic shock (n = 47). Stable isotope bradykinin internal standard was added to samples before solid-phase extraction and quantification by LC-MS/MS. Stability of bradykinin was studied for 12 months. Results: Our assay has good sensitivity (0.1 nmol/l) and a wide linear range (0.1-1000 nmol/1). Bradykinin added to plasma was stable for 12 months at -20 degrees C when a mixture of protease inhibitors was added at sampling but degraded during repeated freezing and thawing. Bradykinin concentration in plasma from septic shock patients (<0.1-0.6 nmol/l) did not change significantly during shock and recovery but differed slightly from that in healthy individuals (0.5-1.1 nmol/1). Conclusions: Our bradykinin assay was successfully used to determine bradykinin concentrations in plasma samples. Intensive care unit patients with septic shock had low concentrations of plasma bradykinin during both shock and recovery phases.